The CTFA Evaluation of Alternatives Program: an evaluation of in vitro alternatives to the Draize primary eye irritation test. (Phase III) surfactant-based formulations

The CTFA Evaluation of Alternatives Program is an evaluation of the relationship between data from the Draize primary eye irritation test and comparable data from a selection of promising in vitro eye irritation tests. In Phase III, data from the Draize test and 41 in vitro endpoints on 25 representative surfactant-based personal care formulations were compared. As in Phase I and Phase II, regression modelling of the relationship between maximum average Draize score (MAS) and in vitro endpoint was the primary approach adopted for evaluating in vitro assay performance. The degree of confidence in prediction of MAS for a given in vitro endpoint is quantified in terms of the relative widths of prediction intervals constructed about the fitted regression curve. Prediction intervals reflect not only the error attributed to the model but also the material-specific components of variation in both the Draize and the in vitro assays. Among the in vitro assays selected for regression modeling in Phase III, the relationship between MAS and in vitro score was relatively well defined. The prediction bounds on MAS were most narrow for materials at the lower or upper end of the effective irritation range (MAS = 0-45), where variability in MAS was smallest. This, the confidence with which the MAS of surfactant-based formulations is predicted is greatest when MAS approaches zero or when MAS approaches 45 (no comment is made on prediction of MAS > 45 since extrapolation beyond the range of observed data is not possible). No single in vitro endpoint was found to exhibit relative superiority with regard to prediction of MAS. Variability associated with Draize test outcome (e.g. in MAS values) must be considered in any future comparisons of in vivo and in vitro test results if the purpose is to predict in vivo response using in vitro data.     

Load Balancing Parallel Explicit State Model Checking

This paper first identifies some of the key concerns about the techniques and algorithms developed for parallel model checking; specifically, the inherent problem with load balancing and large queue sizes resultant in a static partition algorithm. This paper then presents a load balancing algorithm to improve the run time performance in distributed model checking, reduce maximum queue size, and reduce the number of states expanded before error discovery. The load balancing algorithm is based on generalized dimension exchange (GDE). This paper presents an empirical analysis of the GDE based load balancing algorithm on three different supercomputing architectures—distributed memory clusters, Networks of Workstations (NOW) and shared memory machines. The analysis shows increased speedup, lower maximum queue sizes and fewer total states explored before error discovery on each of the architectures. Finally, this paper presents a study of the communication overhead incurred by using the load balancing algorithm, which although significant, does not offset performance gains.     

Factors affecting outcome in hypoxic-ischemic encephalopathy in term infants

Forty-nine term infants were prospectively shown to have hypoxic-ischemic encephalopathy (HIE). All infants survived the neonatal period, and all but two infants (seen at 12 months) were followed up to at least 27 months of age. Factors that significantly correlated with outcome included the Sarnat encephalopathy stage and the occurrence of intractable seizures not controlled by phenobarbital sodium alone. There was no association between the one- or five-minute Apgar score, the need for early ventilation, the EEG, the occurrence of seizures, and the subsequent outcome. There was no significant difference in outcome for those infants who received dexamethasone sodium phosphate (n = 29) v those who did not receive the drug (n = 20). A review of 97 term infants with HIE from a regional perinatal program during a one-year period (1979), including 35 of the 49 infants in the present study, did show a significant increase in morbidity and mortality for transported infants.     

Registration and integration of multiple object views for 3D modelconstruction

Automatic 3D object model construction is important in applications ranging from manufacturing to entertainment, since CAD models of existing objects may be either unavailable or unusable. We describe a prototype system for automatically registering and integrating multiple views of objects from range data. The results can then be used to construct geometric models of the objects. New techniques for handling key problems such as robust estimation of transformations relating multiple views and seamless integration of registered data to form an unbroken surface have been proposed and implemented in the system. Experimental results on real surface data acquired using a digital interferometric sensor as well as a laser range scanner demonstrate the good performance of our system     

Designing for video: investigating the contextual cues within viewing situations

The viewing of video increasingly occurs in a wide range of public and private environments via a range of static and mobile devices. The proliferation of content on demand and the diversity of the viewing situations means that delivery systems can play a key role in introducing audiences to contextually relevant content of interest whilst maximising the viewing experience for individual viewers. However, for video delivery systems to do this, they need to take into account the diversity of the situations where video is consumed, and the differing viewing experiences that users desire to create within them. This requires an ability to identify different contextual viewing situations as perceived by users. This paper presents the results from a detailed, multi-method, user-centred field study with 11 UK-based users of video-based content. Following a review of the literature (to identify viewing situations of interest on which to focus), data collection was conducted comprising observation, diaries, interviews and self-captured video. Insights were gained into whether and how users choose to engage with content in different public and private spaces. The results identified and validated a set of contextual cues that characterise distinctive viewing situations. Four archetypical viewing situations were identified: ‘quality time’, ‘opportunistic planning’, ‘sharing space but not content’ and ‘opportunistic self-indulgence’. These can be differentiated in terms of key contextual factors: solitary/shared experiences, public/private spaces and temporal characteristics. The presence of clear contextual cues provides the opportunity for video delivery systems to better tailor content and format to the viewing situation or additionally augment video services through social media in order to provide specific experiences sensitive to both temporal and physical contexts.     

The trithorax group gene moira encodes a brahma-associated putative chromatin-remodeling factor in Drosophila melanogaster

The genes of the trithorax group (trxG) in Drosophila melanogaster are required to maintain the pattern of homeotic gene expression that is established early in embryogenesis by the transient expression of the segmentation genes. The precise role of each of the diverse trxG members and the functional relationships among them are not well understood. Here, we report on the isolation of the trxG gene moira (mor) and its molecular characterization. mor encodes a fruit fly homolog of the human and yeast chromatin-remodeling factors BAF170, BAF155, and SWI3. mor is widely expressed throughout development, and its 170-kDa protein product is present in many embryonic tissues. In vitro, MOR can bind to itself and it interacts with Brahma (BRM), an SWI2-SNF2 homolog, with which it is associated in embryonic nuclear extracts. The leucine zipper motif of MOR is likely to participate in self-oligomerization; the equally conserved SANT domain, for which no function is known, may be required for optimal binding to BRM. MOR thus joins BRM and Snf5-related 1 (SNR1), two known Drosophila SWI-SNF subunits that act as positive regulators of the homeotic genes. These observations provide a molecular explanation for the phenotypic and genetic relationships among several of the trxG genes by suggesting that they encode evolutionarily conserved components of a chromatin-remodeling complex.     

Validation of highly polymorphic fluorescent multiplex short tandem repeat systems using two generations of DNA sequencers

Validation studies are a crucial requirement before implementation of new genetic typing systems for clinical diagnostics or forensic identity. Two different fluorescence-based multiplex DNA profiling systems composed of amelogenin, HumD21S11 and HumFGA (referred to as multiplex 1A), and HumD3S1358, HumD21S11 and HumFGA (multiplex 1B) have been evaluated for use in forensic identification using the Applied Biosystems Model 373A and Prism 377 DNA Sequencers, respectively. Experiments were aimed at defining the limit of target DNA required for reliable profiling, the level of degradation that would still permit amplification of the short tandem repeat (STR) loci examined, and the robustness of each locus in the multiplexes after samples were exposed to environmental insults. In addition, the specificity of the multiplexes was demonstrated using nonhuman DNAs. Forensically relevant samples such as cigarette butts, chewing gum, fingernails and envelope flaps were processed using both an organic extraction procedure and a QIAamp protocol. DNAs and resultant multiplex STR profiles were compared. The validation of the triplex STR systems was extended to include over 140 nonprobative casework specimens and was followed with a close monitoring of initial casework (over 300 exhibits). Our results document the robustness of these multiplex STR profiling systems which, when combined with other multiplex systems, could provide a power of discrimination of approximately 0.9999.